Bromocriptine as a Potential Glucose-lowering Agent for the Treatment of Prolactinoma with Type 2 Diabetes.

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%. After two months, she was admitted to our hospital and finally diagnosed with prolactinoma. For the treatment of prolactinoma, bromocriptine 2.5 mg/day was started. After seven days, her post-prandial blood glucose levels, homeostasis model assessment of insulin resistance and plasma C-peptide levels were significantly improved. These results indicate that traditional bromocriptine can be an effective therapeutic alternative in patients with prolactinoma complicated with type 2 diabetes.

Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients.

BACKGROUND: Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a therapeutic target for type 2 diabetes (T2DM). Arterial stiffness, a predictor of future cardiovascular events and all-cause mortality, is augmented in these patients. However, effects of DPP-4 inhibitors on arterial stiffness remain unknown. In this study, we compared effects of anagliptin, an inhibitor of DPP-4 on arterial stiffness evaluated by cardio-ankle vascular index (CAVI) with those of an equipotent glucose-lowering agent, glimepiride in patients with T2DM. METHODS: The study involved 50 consecutive outpatients (33 males and 17 females; mean age of 72.5±9.5 years) who visited our hospitals for a risk-screening test or treatment for T2DM. They underwent complete history and physical examination, and determination of blood chemistry and anthropometric variables, and then were randomized to receive either anagliptin (n=26) or glimepiride (n=24) for 6 months. RESULTS: After 6-months treatment, fasting plasma glucose and HbA1c values were comparably reduced in both groups. Anagliptin, but not glimepiride treatment significantly decreased low-density lipoprotein cholesterol, malondialdehyde-modified LDL, remnant-like particle (RLP) cholesterol, CAVI, alanine transaminase (ALT), γ-glutamyl transferase and visceral fat volume. In multiple regression analysis, absolute changes from baseline of RLP cholesterol and ALT after anagliptin treatment for 6 months (ΔRLP cholesterol and ΔALT) were independently correlated with ΔCAVI (R2=0.445). CONCLUSION: The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function.

Age-related changes in the diurnal variation of ketogenesis in patients with type 2 diabetes and relevance to hypoglycemic medications.

To assess the significance of ketogenesis in the management of diabetes mellitus, we analyzed the factors associated with the diurnal variation of the plasma ketone body levels. The subjects consisted of 220 patients with type 2 diabetes, aged 60 ± 15 years, without advanced complications. They ate a standardized, low-fat meal at 8:00, 12:00, and 18:00. The plasma levels of 3-hydroxybutyrate (3HB) and free fatty acid (FFA) were increased before breakfast and before dinner. The plasma glucose concentration was almost the same at any blood sampling time point among age quartiles. However, the 3HB levels were significantly decreased with age, which was most obvious before dinner. The FFA levels also decreased with age, but the decline was mild. A multiple regression analysis with stepwise selection revealed that age was an independent, negative contributor and that the pre-breakfast FFA concentration was an independent, positive contributor to the pre-breakfast 3HB levels. Regarding the pre-dinner 3HB levels, in addition to age and the pre-dinner FFA concentration, the uses of sulfonylurea and dipeptidyl peptidase-4 inhibitors were independent negative contributors. The metabolism of ketone bodies is an alternative energy source for the brain under conditions of starvation. While excessive ketogenesis leads to critical ketoacidosis, inadequate ketone body production could be associated with a propensity to develop neurohypoglycemia in elderly patients treated with insulin secretagogues. Because age-related changes in ketogenesis were the most significant before dinner, attention should be paid not only to fasting but also to the pre-dinner levels of 3HB.

Adding of Sitagliptin on Insulin Therapy Effectively and Safely Reduces a Hemoglobin A1c Level and Glucose Fluctuation in Japanese Patients with Type 2 Diabetes.

Aims. Efficacy and safety of DPP-4 inhibitor, sitagliptin, add-on therapy to insulin were investigated in Japanese patients with type 2 diabetes. Subjects and Methods. Two hundred and sixteen patients (126 men, 65 ± 12 years old, BMI 24.9 ± 4.5, means ± S.D.) who had been treated by insulin alone or insulin combined with other oral hypoglycemic agents (OHAs) were recruited, and sitagliptin was added for 3 months. Results. HbA1c was significantly decreased after 3 months of add-on therapy as a whole (8.56 ± 1.50% to 7.88 ± 1.25%, P < 0.0001). Body weight did not change and insulin dosage was significantly (P < 0.0001) decreased for 3 months. Furthermore, day-to-day glucose variability was significantly reduced (18.3 ± 9.1 to 16.1 ± 8.1%, P < 0.05). In stepwise multiple regression analysis on ΔHbA1c as an outcome variable, the higher baseline HbA1c value and a preserved CPR were selected as significant predictive variables. Fifteen patients complained of mild hypoglycemia without any assistance during 3 months of sitagliptin add-on, while no severe hypoglycemic episode was reported. Conclusions. Add-on of sitagliptin to ongoing insulin therapy effectively reduced either HbA1c level or glucose fluctuation and could be a practical and well-tolerated alternative to treat Japanese patients with type 2 diabetes who had been inadequately controlled by insulin with or without other OHAs.

Prevalence and clinical characteristics of unremembered nocturnal eating in diabetic subjects: Kurume sleep trouble in obesity and metabolic disorders (KUSTOMED) study.

Nighttime food intake is associated with weight gain and higher HbA1c levels. We experienced night eaters who have no memory of their nocturnal eating in the morning. In this study, the curious night eating behavior was designated as "unremembered nocturnal eating syndrome (UNES)". We screened 1,169 patients with diabetes for sleep quality and abnormal eating behavior at night using the Pittsburgh Sleep Quality Index questionnaire with an additional question regarding UNES. When abnormal nocturnal eating behavior was noted, detailed clinical information was extracted from interviews with the patients. We identified 9 patients who experienced UNES. They had a higher BMI compared with subjects who reported no such episodes. Among them, 6 patients who consumed food at night without memory 2-5 times per month or more had significantly higher HbA1c levels. Continuous glucose monitoring in a patient with type 1 diabetes revealed an abrupt elevation of glucose levels from midnight when some foods were consumed. Eight of the 9 patients were taking benzodiazepine and/or non-benzodiazepine hypnotic agents when they experienced the episodes. The prevalence of UNES was 0.8% in all subjects and 4% in those taking hypnotic drugs. The ratio of hypnotic drug use in subjects with UNES was significantly higher than for individuals without UNES (89% vs. 17%, p<0.0001). Although UNES seems to be etiologically heterogeneous, hypnotics-induced parasomnia and/or anterograde amnesia may be associated with the behavior. UNES is not rare in diabetic patients on hypnotic medicine and may be a hidden cause of unexpected morning hyperglycemia.